Identification of B Cell Epitopes of Blo t 13 Allergen and Cross-Reactivity with Human Adipocytes and Heart Fatty Acid Binding Proteins.

Marlon Múnera,Alexis Labrada,Dalgys Martínez,Leonardo Puerta,Luis Caraballo

doi:10.3390/ijms20246107

Abstract

Cross-reactivity between allergens and human proteins could have a clinical impact in allergic diseases. Blo t 13 is an allergen from the mite Blomia tropicalis, which belongs to the fatty acid binding protein (FABP) family and has structural homology with human FABPs. This work aimed to map B cell epitopes on Blo t 13 and to identify epitopes involved in cross-reactivity with human heart FABP (FABP3) and adipocyte FABP (FABP4). Sera from 25 patients with house dust mite (HDM) allergy that were sensitized to Blo t 13 were used for testing the reactivity of immunoglobulin E (IgE) and IgG to FABP. The epitope mapping of Blo t 13 was performed using overlapping peptides, and cross-reactivity between Blo t 13 and human FABP was analyzed using human sera and anti-Blo t 13 monoclonal antibodies. IgE antibodies to all FABPs were detected in 14/25 serum samples, and IgG was detected in 25/25 serum samples. The cross-reactivity of Blo t 13 was 42% with FABP3 and 48% with FABP4. Two IgE-binding regions were identified in Blo t 13; one between residues 54 and 72 (the main cross-reacting region) and another between residues 111 to 129. Our results suggest that exposure to the Blo t 13 allergen could induce an auto-reactive response to endogenous FABP in allergic patients sensitized to Blo t 13.

Highlights

An autoantigen is usually a protein that can be recognized by the immune system of patients suffering from a specific autoimmune response [1]
Several environmental allergens have the capacity to induce an autoimmune response meditated by immunoglobulin E (IgE) antibodies due to their homology with endogenous homologous proteins [2]
It is reasonable to assume that IgE-mediated cross-linking of high-affinity IgE receptor (FcεRI) on effector cells induced by homologous autoantigens can elicit the same symptoms as those induced by environmental allergens, and this could explain exacerbations of chronic allergic diseases in the absence of external exposure [2]

Summary

Introduction

An autoantigen is usually a protein that can be recognized by the immune system of patients suffering from a specific autoimmune response [1]. The clinical relevance of IgE responses to self-antigens remains largely unclear Their capacity to evoke allergic immediate-type reactions and to induce mediator release from basophils and mastocytes of sensitized individuals has been demonstrated. Based on these observations, it is reasonable to assume that IgE-mediated cross-linking of high-affinity IgE receptor (FcεRI) on effector cells induced by homologous autoantigens can elicit the same symptoms as those induced by environmental allergens, and this could explain exacerbations of chronic allergic diseases in the absence of external exposure [2]. Crameri et al [4], using in silico analysis, predicted antigenic regions conserved among cyclophilins from Malassezia sympodialis (allergen: Mala s 6), Aspergillus fumigatus (allergen: Asp f 11), and from humans. An inhibition assay confirmed the presence of cross-reactivity among environmental allergens and homologous endogenous antigens [4]

Objectives

Methods

Results